Diagnostic Accuracy of 2-[18F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults

Abstract

Objectives: To compare the diagnostic accuracy of 2-[¹⁸F]fluoro-2-deoxy-D-glucose-enhanced positron emission tomography (2-[¹⁸F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies.

Methods: In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8 years ± 5.1 [standard deviation]; age range, 7-25 years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[¹⁸F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[¹⁸F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference.

Results: The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[¹⁸F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different "blind spots" for 2-[¹⁸F]FDG-PET and MRI: 2-[¹⁸F]FDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for ¹⁸F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[¹⁸F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[¹⁸F]FDG-PET (96.9%, p < 0.001) or DW-MRI (96.3%, p < 0.001).

Conclusions: Both 2-[¹⁸F]FDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone.

Key points: • DW-MRI and 2-[¹⁸F]FDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors. • Both modalities can miss bone marrow metastases, although the "blind spot" of each modality is different. • A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.

Keywords: 2-[18F]FDG-PET; Bone marrow metastases; Children; DW-MRI; PET/MRI.

Fig. 1.

Flowchart of study design. Among 108 potentially eligible patients who were referred to PET/MR for cancer staging or restaging, 23 patients included in the study and underwent simultaneous 2-[¹⁸F]FDG-PET, DW-MRI scan, and contrast-enhanced MRI. At baseline, 22 simultaneous 2-[¹⁸F]FDG-PET, DW-MRI, and contrast-enhanced MRI scans were included. Following the chemotherapy treatment, 43 simultaneous 2-[¹⁸F]FDG-PET, DW-MRI, and contrast-enhanced MRI scans were performed on the included patients. Abbreviations: PET/MR: positron emission tomography/magnetic resonance, 2-[¹⁸F]FDG-PET: 2-[¹⁸F]fluoro-2-deoxy-D-glucose enhanced positron emission tomography, DW-MRI: Diffusion weighted-magnetic resonance imaging.

Fig. 2.

Concept of integrated 2-[¹⁸F]FDG-PET/MRI and DW-MRI. 2-[¹⁸F]FDG-PET (a) and DW-MRI (b) images were color-encoded (c and e, respectively) and then fused with the contrast-enhanced MRI scan (d) for anatomical orientation, yielding the integrated 2-[¹⁸F]FDG-PET/MRI (f) or DW-MRI (g). Both 2-[¹⁸F]FDG-PET and DW-MRI images visualize a subcentimeter bone marrow metastasis in the left proximal 11^th rib (arrow) in a 25-year-old female patent with Wilms tumor.

Fig. 3.

Quantitative evaluation of the tumor-to-marrow contrast on 2-[¹⁸F]FDG-PET and DW-MRI scans. a 2-[¹⁸F]FDG-PET: Standardized uptake values (SUV) of bone marrow metastases (SUV_max) are significantly higher compared to SUV_mean of normal bone marrow on baseline and post-treatment scans (p< 0.001, respectively). b DW-MRI: Signal-to-noise ratios (SNR) of bone marrow metastases (tumor) are significantly higher compared to SNR of normal bone marrow on baseline and post-treatment scans (p< 0.001, respectively). c The tumor-to-marrow contrast on 2-[¹⁸F]FDG-PET, measured as the difference between the tumor SUV_max and normal bone marrow SUV_mean, was significantly smaller on post-treatment scans compared to baseline scans (p=0.014). The tumor-to-marrow contrast on DW-MRI, measured as the difference between the tumor SNR and normal bone marrow SNR, was not statistically significant between baseline and post-treatment scans (p=0.118). Baseline data are displayed as mean values of 62 true positive lesions on 2-[¹⁸F]FDG-PET and 57 true positive lesions on DW-MRI plus standard deviations. Post-treatment data are displayed as mean values of 139 true positive lesions on 2-[¹⁸F]FDG-PET and 140 true positive lesions on DW-MRI plus standard deviations.

Fig. 4.

Improved detection of a bone marrow metastasis in a 22-year-old male patient with diffuse large B-cell lymphoma on 2-[¹⁸F]FDG-PET compared to DW-MRI. Baseline scans (a-f), A bone marrow metastasis in the third thoracic vertebra (yellow arrow) demonstrates high FDG uptake on 2-[¹⁸F]FDG-PET (a). The lesion is not visible on the contrast enhanced MRI (b). The combined 2-[¹⁸F]FDG-PET/MR scan localized the lesion to the vertebral body (c). The simultaneously acquired DW-MRI does not show the bone lesion because of local susceptibility artifacts (d). The lesion is also not visible on the contrast enhanced MRI (e). Therefore, the combined DW-MRI scan does not show the lesion either (f). Follow up scans after 2 weeks of chemotherapy (g-l), The bone marrow lesion demonstrates decreased FDG uptake on the 2-[¹⁸F]FDG-PET scan (g), consistent with therapy response. The lesion now demonstrates contrast enhancement on the gadolinium chelate enhanced MRI scan (h), a typical feature of treated bone marrow lesions in patients with lymphoma. The lesion can be detected on the integrated 2-[¹⁸F]FDG-PET/MRI scan (i). The simultaneously acquired DW-MRI (j) now shows the bone lesion as an area of restricted diffusion (yellow arrow). When fused with the gadolinium chelate enhanced MRI scan (k), the lesion can be equally well detected as on the integrated DW-MRI scan (l). Note that the patient also has a mediastinal lymph node (white arrow).

Fig. 5.

Improved detection of a bone marrow metastasis in an 18-year-old male patient with Ewing sarcoma on DW-MRI compared to 2-[¹⁸F]FDG-PET scan. Baseline scans (a-f), A bone marrow metastasis in the right iliac wing (arrow) demonstrates minor 2-[¹⁸F]FDG uptake on the PET scan (a). The lesion is also noted on the contrast-enhanced T1-weighted gradient echo scan (b) and the integrated 2-[¹⁸F]FDG-PET/MRI (c). The same bone marrow metastasis (arrow) demonstrates markedly restricted diffusion on the DW-MRI (d). After fusion with the contrast-enhanced MRI (e), it is better depicted on the integrated DW-MRI (f) than on the integrated 2-[¹⁸F]FDG-PET/MR scan. Follow up scans after 9 weeks of chemotherapy (g-l), On the post-treatment 2-[¹⁸F]FDG-PET scan (g), the normal bone marrow demonstrates increased hypermetabolic activity, which obscures the lesion (yellow arrow). The contrast-enhanced MRI demonstrates a larger area of inhomogeneous enhancement (h). It is difficult to determine a change in size or metabolic activity based on the integrated 2-[¹⁸F]FDG-PET/MRI (i). However, the DW-MRI scan (j) clearly demonstrates that the lesion increased in size. After fusion with the contrast-enhanced MRI (k), the integrated DW-MRI clearly demonstrates interval tumor growth (l). This case demonstrates that DW-MRI can sometimes better depict tumor progression than 2-[¹⁸F]FDG-PET.